text: Circulating tumour DNA (ctDNA) molecules are tumour-derived cell-free DNA (cfDNA) circulating in the bloodstream and are not associated with cells. CtDNA primarily arises from chromatin fragmentation accompanying tumour cell death and can be extracted by liquid biopsy. CtDNA analysis has been implemented for noninvasive identification of tumour genetic characteristics and early recognition of various cancer forms. The majority of current ctDNA analysis depends on genetic differences in germline or somatic cells to diagnose diseases and detect tumour cells at an early stage. While looking at genetic variations of ctDNA can be beneficial, not all ctDNAs contain genetic mutations. EPIC-seq unitized epigenetic features of ctDNA to inform tissue-of-origin of these unmutated molecules, which is helpful for cancer classification.